title: Resveratrol exacerbates both autoimmune and viral models of multiple sclerosis.
abstract: The polyphenol compound resveratrol is reported to have multiple functions, including neuroprotection, and no major adverse effects have been reported. Although the neuroprotective effects have been associated with sirtuin 1 activation by resveratrol, the mechanisms by which resveratrol exerts such functions are a matter of controversy. We examined whether resveratrol can be neuroprotective in two models of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). EAE was induced in C57BL/6 mice, which were fed a control diet or a diet containing resveratrol during either the induction or effector phase or through the whole course of EAE. SJL/J mice were infected with TMEV and fed a control diet or a diet containing resveratrol during the chronic phase of TMEV-IDD. In EAE, all groups of mice treated with resveratrol had more severe clinical signs than the control group. In particular, resveratrol treatment during the induction phase resulted in the most severe EAE, both clinically and histologically. Similarly, in the viral model, the mice treated with resveratrol developed significantly more severe TMEV-IDD than the control group. Thus, surprisingly, the resveratrol treatment significantly exacerbated demyelination and inflammation without neuroprotection in the central nervous system in both models. Our findings indicate that caution should be exercised in potential therapeutic applications of resveratrol in human inflammatory demyelinating diseases, including multiple sclerosis.
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Sato
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Martinez
authors.affiliation: Dow Medical College, Karachi, Pakistan.
authors.forename: Maira
authors.initials: M
authors.lastname: Shahid
authors.affiliation: Neurovirology Research Laboratory, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah; Department of Neurology, Brain Institute, University of Utah, Salt Lake City, Utah.
authors.forename: John W
authors.initials: JW
authors.lastname: Rose
authors.affiliation: Neurovirology Research Laboratory, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah; Department of Neurology, Brain Institute, University of Utah, Salt Lake City, Utah; Geriatric Research Education and Clinical Center, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah; Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah.
authors.forename: Noel G
authors.initials: NG
authors.lastname: Carlson
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana. Electronic address: itsuno@lsuhsc.edu.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tsunoda
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000187:drug effects*; D001369:Axons / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000150:complications / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D009410:Nerve Degeneration / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000821:virology; D018696:Neuroprotective Agents / Q000009:adverse effects; D000077185:Resveratrol; D013267:Stilbenes / Q000009:adverse effects*; D017945:Theilovirus / Q000472:pathogenicity / Q000502:physiology*; D014774:Virulence
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein; D018696:Neuroprotective Agents; D013267:Stilbenes; D000077185:Resveratrol